PDGFR mutants bind type II TKIs

Stable Identifier
R-HSA-9674430
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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Imatinib and other type II tyrosine kinase inhibitors bind to the inactive conformation of the PDGF receptors at site near the ATP-binding site that is not present in the active conformation (reviewed in Klug et al, 2018). Juxtamembrane domain mutants of PDGFRA such as V561D relieve the autoinhibition of the receptor without completely driving the equilibrium to the fully active form; as a result, juxtamembrane mutants tend to be sensitive to type II TKIs. Mutations in the activation loop, in contrast, much more strongly shift the equilibrium of the protein toward the active state, and mutations in this region, such as the most prevalent D842V, tend to be resistant to type II TKIs (reviewed in Roskoski, 2018; Klug et al, 2018)

Literature References
Participants
Participant Of
Normal reaction
Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
Authored
Reviewed
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